Stancu Harmon Tiedman Sandbox 12

The Mechanism of Trypsin
Trypsin is a very important enzyme in the digestive system that catalyzes the cleavage of peptide bonds. Its active site interacts with the substrate to promote cleavage; specifically three residues are primarily responsible for trypsin's catalytic ability.

The structure of trypsin is characterized by an active site with a catalytic triad His- Asp- Ser (residue numbers 57, 102 and 195)(pdb 2agi). The His 57 acts as a proton acceptor for the Ser 195, activating the nucleophilic attack at the carbonyl group on incident proteins. Asp 102 further stabilizes the histidine residue through hydrogen bonding. The specificity of the active site pocket is characterized by the presence of an anionic Asp residue, 189, used to create ionic interactions to accommodate bulky side chains like Arg and Lys from the other protein

Trypsin favors the intermediate state, so it breaks the peptide bond and releases the amino group while retaining the carbonyl carbon. Then the same process repeats except this time His 57 picks up a hydrogen from water and the remaining OH attacks the carbonyl carbon from the original peptide. The Serine 195 then picks up the Hydrogen from His 57, the electrons from the negatively charged oxygen move down causing the molecule to be released from Serine. It is the specific location of Ser, His, and Asp that allow them to function together so well. This catalytic ability of trypsin would be lost if the structure of the molecule changed in anyway to disturb these three residues at the active site.